Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease
Open accessAbstract
Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.
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A decrease of short chain fatty acid levels, and of genes related to short chain fatty acid metabolism, is described in Crohn's disease.
“In addition, a decrease of SCFA levels, and of genes related to SCFA metabolism, is described in CD [41] .”
From Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis (2014) · cites this paper as [41]
The IBD metagenome contains 25% fewer genes than the healthy gut with metaproteomic studies showing a correlative decrease in proteins and functional pathways.
“The IBD metagenome contains 25% fewer genes than the healthy gut with metaproteomic studies showing a correlative decrease in proteins and functional pathways.69”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [69]
Ileal CD has been shown to be associated with alterations in bacterial carbohydrate metabolism and bacterial-host interactions, as well as human host-secreted enzymes.
“Specifically, ileal CD has been shown to be associated with alterations in bacterial carbohydrate metabolism and bacterial-host interactions, as well as human host-secreted enzymes.69”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [69]
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- Authors
- Erickson, A. R., Cantarel, B. L., Lamendella, R., Darzi, Y., Mongodin, E. F., Pan, C., Shah, M., Halfvarson, J., Tysk, C., Henrissat, B., Raes, J., Verberkmoes, N. C., Fraser, C. M., Hettich, R. L., & Jansson, J. K.
- Affiliations
- Oak Ridge National Laboratory (US)
- University of Maryland, Baltimore (US)
- Lawrence Berkeley National Laboratory (US)
- Vrije Universiteit Brussel (BE)
- Örebro University (SE)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Jansson, Janet K.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-11-28
- Volume
- 7
- Issue
- 11
- Pages
- e49138
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3509130
- OpenAlex
- W2097804645
- Cited by
- 395
- References
- 65
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 17 · 2023: 12 · 2022: 17 · 2021: 20 · 2020: 26 · 2019: 51 · 2018: 33 · 2017: 41 · 2016: 54 · 2015: 37 · 2014: 43 · 2013: 29 · 2012: 2
- FWCI
- 14.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- National Institutes of Health (UH2DK83991)
- National Institute of Diabetes and Digestive and Kidney Diseases (UH2DK83991, UH2DK083991)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- Crohn's disease, gut microbiota, metagenomics, metaproteomics, inflammatory bowel disease, ileal Crohn's disease, colonic Crohn's disease, twin pairs, bacterial carbohydrate metabolism, host-bacteria interactions, diagnostic biomarkers, functional signatures
- MeSH terms
- Bacteria, Crohn Disease, Female, Humans, Ileum, Intestinal Mucosa, Male, Twins, Monozygotic, Cluster Analysis, Proteome, Proteomics, Gastrointestinal Tract, Metabolic Networks and Pathways, Metagenome, Metagenomics
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